The purpose of this study is to assess the effects of prenatal and early childhood exposure to environmental tobacco smoke (ETS) on brain structure and function in a cohort of inner-city children who are 9-10 years of age. The proposed work builds on, and shares a cohort with, a prospective cohort study of ambient air pollutant effects on child development and respiratory health, currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) (P.I. Perera, RO1 ES08977 NIEHS: 8/01/07-5/31/12; NIEHS P50 ES09066, EPA R827027:11/1/03-10/31/08). Previous findings from the CCCEH cohort study have shown that prenatal exposure to ETS was associated with an increased risk of cognitive disturbances at age 2 years (Rauh et al., 2004) and increased risk of ADHD-like symptoms at age 2-3 years (Rauh et al., 2006). These findings suggest the concerning presence of disturbances of cognition, inattention, hyperactivity, and impulse control associated with early exposure to ETS. Consistent with these behavioral findings, our pilot MRI data comparing the brains of 15 children prenatally exposed to ETS with 15 unexposed children showed significant effects on regional brain volumes and anatomical connectivity at 5-7 years of age, regardless of their degree of postnatal exposure. Based on these preliminary findings, we propose to evaluate the effects of prenatal and early childhood exposure to ETS on brain development and cognitive functioning in 250 children at 9-10 years of age. We will use Magnetic Resonance Imaging (MRI) to study detailed brain anatomy, fiber tracts, and metabolites in these children, and we will assess cognitive and attentional functioning using an array of neuropsychological tasks. ETS was selected as a model agent for translational research because it is well characterized, well-studied in animals, and continues to be a highly prevalent exposure. Specifically, we propose to: (1) assess the 9-10-year effects of prenatal and early childhood exposures to ETS on neurobehavioral (inattention, hyperactivity) and neuropsychological functioning (attentional capacity, memory, impulse control and sensory motor functioning); and (2) assess the 9-10-year effects of prenatal and early childhood exposures to ETS on measures of brain structure (using anatomical MRI), brain chemistry (using magnetic resonance spectroscopy), and anatomical connectivity (using diffusion tensor imaging), and functional activity (using fMRI) in the same children. PUBLIC HEALTH RELEVANCE: This application is for a 5-year study to assess the effects of exposure to environmental tobacco smoke on brain development (assessed by MRI and fMRI) and neurobehavioral functioning (assessed by standardized clinical and developmental testing) in a cohort of 250 inner-city children who have reached 9-10 years of age. This work shares a cohort with a longitudinal study of ambient air pollutant effects on child development, from the prenatal period to 11 years of age, being conducted by the Columbia Center for Children's Environmental Health. The project has access to previously collected biomarkers of exposure and rich socio-demographic data throughout childhood.